Canadian Researchers Battling Drug-Resistant Bacteria

Drug resistance is an alarming prospect in both human and equine medicine, particularly because researchers are recognizing an ever-increasing number of disease-causing organisms (or pathogens) resistant to common antibiotics. Some that cause disease in horses include Staphylococcus aureus, Escherichia coli, and Rhodoccocus equi, to name a few.

“Given their fast generation times (on the scale of minutes instead of our years), bacteria are able to adapt and evolve very quickly to their changing environments, and it this ability that allows them to develop or acquire resistance to the antibiotics that we challenge them with,” explained Anthony Clarke, PhD, a professor in the Department of Molecular and Cellular Biology, at the University of Guelph, in Ontario, Canada.

“The overuse and abuse of our antibiotics in the past has exacerbated this such that highly-resistant, so-called ‘superbugs,’ now exist that are resistant to almost all antibiotics available to the clinicians," he added. "Consequently, we have to manage our current arsenal of antibiotics carefully while continually trying to stay a step or two ahead of them with the search for and development of new drugs.”

Several research groups have spent years attempting to identify new “targets” that can be used to control bacterial infections (by either arresting the growth or killing bacteria cells outright). A series of studies resulted in the identification of a specific class of enzyme called “Ape.” Those enzymes play an integral role in modifying the cell wall of certain bacteria to control their metabolism. In addition, researchers identified a plant product called “purpurin” as a natural antibacterial agent that functions by inhibiting Ape.

“To take this research to the next level in developing new antibiotics, we need to obtain detailed information regarding the three-dimensional structure and function of Ape; however, three separate research groups previously attempted to achieve this but were unsuccessful,” Clarke said.

Building on others’ research and using laboratory techniques to change very specific components of Ape, Clarke and colleagues identified key amino acids—building blocks that make up Ape—that contribute to its shape and function.

“Our research has contributed to an additional understanding of Ape and will facilitate the search and/or design of new antibacterials; however, we still need a three-dimensional ‘image’ of Ape for the rational design of more potent inhibitors which may prove to be lead compounds for a new class of antibiotics,” noted Clarke.

Although this research was performed on the bacterium that causes gonorrhea, the bacterial cell wall component under study, called peptidoglycan, is common to almost all bacteria and already serves as the target for a number of important antibiotic classes used in horses, including the penicillins and cephalosporins.

Clarke concluded, “Like these other antibiotics, inhibitors targeting Ape would have a broad spectrum of activity against many pathogenic bacteria.”

The study, “Mechanism of action of Neisseria gonorrhoeae O-acetylpeptidoglycan esterase, an SGNH serine esterase,” was published in the Journal of Biological Chemistry. The study was co-authored by former doctoral students John Pfeffer and Joel Weadge.

About the Author

Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.

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